OBJECTIVES: L-[3-(18)F]-alpha-methyltyrosine ((18)F-FMT) is an amino-acid tracer for positron emission tomography (PET) and is used for tumor detection because malignant tumor cells accumulate (18)F-FMT based on the increased expression of an amino-acid transporter. This study was conducted to investigate the usefulness of (18)F-FMT PET in combination with fluorine-18-fluorodeoxyglucose ((18)F-FDG) PET for the diagnosis of sarcoidosis in patients with suspected malignancy. SETTING: Twenty-four sarcoidosis patients with suspected malignancy underwent (18)F-FDG and (18)F-FMT PET. The study included 17 patients with extrapulmonary manifestation mimicking malignant disease (13 patients with systemic lymphadenopathy, 3 of them with concomitant hepatosplenic processes; 3 patients with hepatosplenic processes without concomitant lymphadenopathy; and 1 patient with multiple bone lesions), 3 patients with occurrence of bilateral hilar lymphadenopathy in cancer patients, and 4 patients with multiple nodules mimicking pulmonary metastasis. RESULTS: All patients showed increased uptake of (18)F-FDG and no increase in the accumulation of (18)F-FMT in their lymphadenopathy. Standardized uptake values (SUVs) of (18)F-FDG and (18)F-FMT were 5.01 +/- 2.15 and 0.77 +/- 0.24, respectively (mean +/- SD). All extranodal lesions such as liver, spleen, and bone were visually positive on (18)F-FDG PET and negative on (18)F-FMT PET. No neoplasm was confirmed in all patients. In a control group of patients with lung cancer, SUVs for (18)F-FDG and (18)F-FMT were 6.34 +/- 2.52 and 1.54 +/- 0.82, respectively. CONCLUSION: The uptake of (18)F-FDG was positive in the sarcoid lesions, and therefore (18)F-FDG PET could not differentiate sarcoidosis from malignant disease. Use of (18)F-FMT PET in combination with (18)F-FDG PET may be the effective method to distinguish sarcoidosis from malignancy.